tbuckley/cabot-search huggingface dataset:
Autologous hematopoietic stem cell transplantation for a patient with multiple autoimmune diseases
Authors: Pongthep Vittayawacharin, Michael Y. Sy, Sanaz Attaripour Isfahani, William E. Karnes, Piyanuch Kongtim, Stefan O. Ciurea
Journal: American Journal of Hematology (2023)

Level of autoantibodies after autologous hematopoietic stem cell transplantation. AGA, antigliadin antibody; AHSCT, autologous hematopoietic stem cell transplantation; Anti-GAD65, Ab anti-glutamic acid decarboxylase epitope 65 antibody; Anti-TPO, anti-thyroid peroxidase antibody; CU, chemiluminescent unit.
Highly Tough and Biodegradable Poly(ethylene glycol)‐Based Bioadhesives for Large‐Scaled Liver Injury Hemostasis and Tissue Regeneration
Authors: Yiqian Huang, Wei Jing, Jianping Zeng, Yunxia Xue, Yan Zhang, Xueqiao Yu, Pengfei Wei, Bo Zhao, Jiahong Dong
Journal: Advanced Healthcare Materials (2023)

Abstract Conventional tissue adhesives face challenges for hemostasis and tissue regeneration in large‐scaled hemorrhage and capillary hypobaric bleeding due to weak adhesion, and inability to degrade at specific sites. Herein, convenient and injectable poly(ethylene glycol) (PEG)‐based adhesives are developed to address the issues for liver hemostasis. The PEG‐bioadhesives are composed of tetra‐armed PEG succinimide glutarate (PEG‐SG), tetra‐armed PEG amine (PEG‐NH 2 ), and tri‐lysine. By mixing the components, the PEG‐bioadhesives can be rapidly formulated for use of liver bleeding closure in hepatectomy. The PEG‐bioadhesives also possess mechanical compliance to native tissues (elastic modulus ≈40 kPa) and tough tissue adhesion (≈28 kPa), which enables sufficient adhering to the injured tissues and promotes liver regeneration with the PEG‐bioadhesive degradation. In both rats of liver injury and pigs of large‐scaled hepatic hemorrhage, the PEG‐bioadhesives show effective hemostasis with superior blood loss than conventional tissue adhesives. Due to biocompatibility and degradability, the PEG‐bioadhesive is advantageous for liver regeneration, while commercial adhesives (e.g., N ‐octyl cyanoacrylate) display adhesion failure and limited liver reconstructions. These PEG‐bioadhesive components are FDA‐approved, and demonstrate excellent adhesion to various tissues not only for liver hemostasis, it is a promising candidate in biomedical translations and clinical applications.
Disparities in breast cancer among patients with disabilities: care gaps, accessibility, and best practices
Authors: Grace Keegan, John-Ross Rizzo, Kathie-Ann Joseph
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Pronounced disparities exist in detecting and treating breast cancer in women with disabilities, leading to cancer detection at advanced stages. This paper provides an overview of disparities for women with disabilities related to breast cancer screening and care, primarily focusing on clinically significant mobility disabilities. Current care gaps include screening barriers related to accessibility and inequitable treatment options, with race and ethnicity, socioeconomic status, geographic location, and disability severity factors mediating the disparities for this population. The reasons for these disparities are myriad and stem from both system-level deficiencies and individual-level clinician bias. Although structural changes are warranted, individual healthcare professionals must also be incorporated into the requisite change. Intersectionality is critical to disparities and inequities and should be central to any discussion of strategies for improving care for people with disabilities, many of whom have intersectional identities. Efforts to reduce screening rate disparities for breast cancer in women with mobility-related disabilities should start with improving accessibility through removing structural barriers, establishing comprehensive accessibility standards, and addressing healthcare professional bias. Future interventional studies are needed to implement and assess the value of programs to improve breast cancer screening rates in women with disabilities. Increasing the representation of women with disabilities in clinical trials may provide another avenue for reducing treatment disparities because these trials often provide breakthrough treatment to women with cancer diagnosed at later stages. Ultimately, attention to the specific needs of patients with disabilities should be improved across the United States to promote inclusive and effective cancer screening and treatment.
Understanding structure activity relationships of Good HEPES lipids for lipid nanoparticle mRNA vaccine applications
Authors: Rebecca L. Goldman, Namratha Turuvekere Vittala Murthy, Trent P. Northen, Anuranjani Balakrishnan, Sudha Chivukula, Hillary Danz, Timothy Tibbitts, Anusha Dias, Jorel Vargas, Dustin Cooper, Hardip Gopani, Angela Beaulieu, Kirill V. Kalnin, Timothy Plitnik, Saswata Karmakar, Ramesh Dasari, Ryan Landis, Shrirang Karve, Frank DeRosa
Journal: Biomaterials (2023)

Lipid nanoparticles (LNPs) have shown great promise as delivery vehicles to transport messenger ribonucleic acid (mRNA) into cells and act as vaccines for infectious diseases including COVID-19 and influenza. The ionizable lipid incorporated within the LNP is known to be one of the main driving factors for potency and tolerability. Herein, we describe a novel family of ionizable lipids synthesized with a piperazine core derived from the HEPES Good buffer. These ionizable lipids have unique asymmetric tails and two dissimilar degradable moieties incorporated within the structure. Lipids tails of varying lengths, degrees of unsaturation, branching, and the inclusion of additional ester moieties were evaluated for protein expression. We observed several key lipid structure activity relationships that correlated with improved protein production in vivo, including lipid tails of 12 carbons on the ester side and the effect of carbon spacing on the disulfide arm of the lipids. Differences in LNP physical characteristics were observed for lipids containing an extra ester moiety. The LNP structure and lipid bilayer packing, visualized through Cryo-TEM, affected the amount of protein produced in vivo. In non-human primates, the Good HEPES LNPs formulated with an mRNA encoding an influenza hemagglutinin (HA) antigen successfully generated functional HA inhibition (HAI) antibody titers comparable to the industry standards MC3 and SM-102 LNPs, demonstrating their promise as a potential vaccine.
Posttranslational splicing modifications as a key mechanism in cytarabine resistance in acute myeloid leukemia
Authors: María Luz Morales, Roberto García-Vicente, Alba Rodríguez-García, Armando Reyes-Palomares, África Vincelle-Nieto, Noemí Álvarez, Alejandra Ortiz-Ruiz, Vanesa Garrido-García, Alicia Giménez, Gonzalo Carreño-Tarragona, Ricardo Sánchez, Rosa Ayala, Joaquín Martínez-López, María Linares
Journal: Leukemia (2023)

Abstract Despite the approval of several drugs for AML, cytarabine is still widely used as a therapeutic approach. However, 85% of patients show resistance and only 10% overcome the disease. Using RNA-seq and phosphoproteomics, we show that RNA splicing and serine-arginine-rich (SR) proteins phosphorylation were altered during cytarabine resistance. Moreover, phosphorylation of SR proteins at diagnosis were significantly lower in responder than non-responder patients, pointing to their utility to predict response. These changes correlated with altered transcriptomic profiles of SR protein target genes. Notably, splicing inhibitors were therapeutically effective in treating sensitive and resistant AML cells as monotherapy or combination with other approved drugs. H3B-8800 and venetoclax combination showed the best efficacy in vitro, demonstrating synergistic effects in patient samples and no toxicity in healthy hematopoietic progenitors. Our results establish that RNA splicing inhibition, alone or combined with venetoclax, could be useful for the treatment of newly diagnosed or relapsed/refractory AML.
Author correction to ‘TMEM16A inhibits angiotensin II-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner’ [Acta Pharmaceutica Sinica B 11 (2021) 3994–4007]
Authors: Huaqing Zheng, Xiaolong Li, Xin Zeng, Chengcui Huang, Mingming Ma, Xiaofei Lv, Yajuan Zhang, Lu Sun, Guanlei Wang, Yanhua Du, Yongyuan Guan
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2021.04.013.].
Natural history, predictors of development of extramedullary disease, and treatment outcomes for patients with extramedullary multiple myeloma
Authors: Saurabh Zanwar, Matthew Ho, Yi Lin, Prashant Kapoor, Moritz Binder, Francis K. Buadi, Angela Dispenzieri, David Dingli, Amie Fonder, Morie A. Gertz, Wilson Gonsalves, Suzanne R. Hayman, Yi Hwa, Miriam Hobbs, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Eli Muchtar, Rahma Warsame, Dragan Jevremovic, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar
Journal: American Journal of Hematology (2023)

Abstract Extramedullary multiple myeloma (EMM) can present either at initial diagnosis (de novo) or at disease relapse (secondary) and confers an aggressive clinical course. Limited data exist for choosing the optimal therapy for EMM and this remains an area of unmet clinical need. After excluding paraskeletal multiple myeloma and primary plasma cell leukemia, we identified 204 (68%) patients with secondary EMM and 95 (32%) with de novo EMM between January 01, 2000 and 31 December, 2021. The median overall survival (OS) was 0.7 (95% CI: 0.6–0.9) years for secondary EMM and 3.6 (95%CI: 2.4–5.6) years for de novo EMM. The median progression‐free survival (PFS) with initial therapy was 2.9 months (95% CI: 2.4–3.2 months) for secondary EMM and 12.9 months (95% CI: 6.7–18 months) for de novo EMM. Patients with secondary EMM treated with CAR‐T therapy ( n = 20) achieved a partial response (PR) or better in 75% with a median PFS of 4.9 months (3.1 months‐not reached; NR). Patients with EMM treated with bispecific antibodies ( n = 12) achieved a ≥ PR in 33%, with a median PFS of 2.9 months (95%CI: 2.2 months‐NR). In a matched cohort, multivariate logistic regression analysis demonstrated younger age at diagnosis, 1q duplication, and t (4;14) at diagnosis of MM to be independent predictors of development of secondary EMM. Presence of EMM was independently associated with inferior OS in the matched cohorts for both de novo (HR 2.9 [95% CI: 1.6–5.4], p = .0007) and secondary EMM (HR 1.5 [95% CI: 1.1–2], p = .001).
MET Fusions in NSCLC: Clinicopathologic Features and Response to MET Inhibition
Authors: Richard Riedel, Jana Fassunke, Andreas H. Scheel, Matthias Scheffler, Carina Heydt, Lucia Nogova, Sebastian Michels, Rieke N. Fischer, Anna Eisert, Heather Scharpenseel, Felix John, Lea Ruge, Diana Schaufler, Janna Siemanowski, Michaela A. Ihle, Svenja Wagener-Ryczek, Roberto Pappesch, Jan Rehker, Anne Bunck, Carsten Kobe, Felix Keil, Sabine Merkelbach-Bruse, Reinhard Büttner, Jürgen Wolf
Journal: Journal of Thoracic Oncology (2023)
Identification of circulating T‐cell immunoglobulin and mucin domain 4 as a potential biomarker for coronary heart disease
Authors: Mengyao Wang, Ke Gong, Xinran Zhu, Shasha Chen, Jie Zhou, Hui Zhang, Jihong Han, Likun Ma, Yajun Duan
Journal: MedComm (2023)

Efferocytosis, the process of engulfing and removing apoptotic cells, is attenuated in vulnerable plaques of advanced atherosclerosis. T-cell immunoglobulin and mucin domain 4 (TIMD4) is a recognition receptor protein for efferocytosis that has been implicated in atherosclerosis mouse models. However, the role of serum-soluble TIMD4 (sTIMD4) in coronary heart disease (CHD) remains unknown. In this study, we analyzed serum samples collected from two groups: Group 1 (36 healthy controls and 70 CHD patients) and Group 2 (44 chronic coronary syndrome [CCS]) and 81 acute coronary syndrome [ACS] patients). We found that sTIMD4 levels in patients with CHD were significantly higher than those in healthy controls and were also higher in ACS than in CCS patients. The area under the receiver operating characteristic curve was 0.787. Furthermore, our in vitro results showed that low-density lipoprotein/lipopolysaccharide activated p38 mitogen-activated protein kinase, which in turn enhanced a disintegrin and metalloproteinase 17, resulting in increased secretion of sTIMD4. This impairment of macrophage efferocytosis promoted inflammation. Thus, this study is not only the first identification of a potential novel biomarker of CHD, sTIMD4, but also demonstrated its pathogenesis mechanism, providing a new direction for the diagnosis and treatment of CHD.
Inferring Human Immunodeficiency Virus 1 Proviral Integration Dates With Bayesian Inference
Authors: Bradley R Jones, Jeffrey B Joy
Journal: Molecular Biology and Evolution (2023)

Abstract Human immunodeficiency virus 1 (HIV) proviruses archived in the persistent reservoir currently pose the greatest obstacle to HIV cure due to their evasion of combined antiretroviral therapy and ability to reseed HIV infection. Understanding the dynamics of the HIV persistent reservoir is imperative for discovering a durable HIV cure. Here, we explore Bayesian methods using the software BEAST2 to estimate HIV proviral integration dates. We started with within-host longitudinal HIV sequences collected prior to therapy, along with sequences collected from the persistent reservoir during suppressive therapy. We built a BEAST2 model to estimate integration dates of proviral sequences collected during suppressive therapy, implementing a tip date random walker to adjust the sequence tip dates and a latency-specific prior to inform the dates. To validate our method, we implemented it on both simulated and empirical data sets. Consistent with previous studies, we found that proviral integration dates were spread throughout active infection. Path sampling to select an alternative prior for date estimation in place of the latency-specific prior produced unrealistic results in one empirical data set, whereas on another data set, the latency-specific prior was selected as best fitting. Our Bayesian method outperforms current date estimation techniques with a root mean squared error of 0.89 years on simulated data relative to 1.23–1.89 years with previously developed methods. Bayesian methods offer an adaptable framework for inferring proviral integration dates.
Patient-Reported Outcome Measure Use in Guidelines Published by the American Academy of Ophthalmology
Authors: Caberry W. Yu, Keean Nanji, Amin Hatamnejad, Mohamed Gemae, Ishraq Joarder, Abhishek Achunair, Tahira Devji, Mark Phillips, Dena Zeraatkar, David H. Steel, Robyn H. Guymer, Sobha Sivaprasad, Charles C. Wykoff, Varun Chaudhary
Journal: Ophthalmology (2023)
Three‐dimensional genome structure and function
Authors: Hao Liu, Hsiangyu Tsai, Maoquan Yang, Guozhi Li, Qian Bian, Gang Ding, Dandan Wu, Jiewen Dai
Journal: MedComm (2023)

Abstract Linear DNA undergoes a series of compression and folding events, forming various three‐dimensional (3D) structural units in mammalian cells, including chromosomal territory, compartment, topologically associating domain, and chromatin loop. These structures play crucial roles in regulating gene expression, cell differentiation, and disease progression. Deciphering the principles underlying 3D genome folding and the molecular mechanisms governing cell fate determination remains a challenge. With advancements in high‐throughput sequencing and imaging techniques, the hierarchical organization and functional roles of higher‐order chromatin structures have been gradually illuminated. This review systematically discussed the structural hierarchy of the 3D genome, the effects and mechanisms of cis‐regulatory elements interaction in the 3D genome for regulating spatiotemporally specific gene expression, the roles and mechanisms of dynamic changes in 3D chromatin conformation during embryonic development, and the pathological mechanisms of diseases such as congenital developmental abnormalities and cancer, which are attributed to alterations in 3D genome organization and aberrations in key structural proteins. Finally, prospects were made for the research about 3D genome structure, function, and genetic intervention, and the roles in disease development, prevention, and treatment, which may offer some clues for precise diagnosis and treatment of related diseases.
Disrupted epithelial permeability as a predictor of severe <scp>COVID</scp>‐19 development
Authors: Duygu Yazici, Eren Cagan, Ge Tan, Manru Li, Evan Do, Ozan C. Kucukkase, Abdurrahman Simsek, Muhammed Ali Kizmaz, Tugce Bozkurt, Tamer Aydin, Anja Heider, Beate Rückert, Marie‐Charlotte Brüggen, Raja Dhir, Liam O'Mahony, Mubeccel Akdis, Kari C. Nadeau, Ferah Budak, Cezmi A. Akdis, Ismail Ogulur
Journal: Allergy (2023)

An impaired epithelial barrier integrity in the gastrointestinal tract is important to the pathogenesis of many inflammatory diseases. Accordingly, we assessed the potential of biomarkers of epithelial barrier dysfunction as predictive of severe COVID-19.Levels of bacterial DNA and zonulin family peptides (ZFP) as markers of bacterial translocation and intestinal permeability and a total of 180 immune and inflammatory proteins were analyzed from the sera of 328 COVID-19 patients and 49 healthy controls.Significantly high levels of circulating bacterial DNA were detected in severe COVID-19 cases. In mild COVID-19 cases, serum bacterial DNA levels were significantly lower than in healthy controls suggesting epithelial barrier tightness as a predictor of a mild disease course. COVID-19 patients were characterized by significantly elevated levels of circulating ZFP. We identified 36 proteins as potential early biomarkers of COVID-19, and six of them (AREG, AXIN1, CLEC4C, CXCL10, CXCL11, and TRANCE) correlated strongly with bacterial translocation and can be used to predict and discriminate severe cases from healthy controls and mild cases (area under the curve (AUC): 1 and 0.88, respectively). Proteomic analysis of the serum of 21 patients with moderate disease at admission which progressed to severe disease revealed 10 proteins associated with disease progression and mortality (AUC: 0.88), including CLEC7A, EIF4EBP1, TRANCE, CXCL10, HGF, KRT19, LAMP3, CKAP4, CXADR, and ITGB6.Our results demonstrate that biomarkers of intact or defective epithelial barriers are associated with disease severity and can provide early information on the prediction at the time of hospital admission.
Shotgun metagenomic sequencing on skin microbiome indicates dysbiosis exists prior to the onset of atopic dermatitis
Authors: Prem Prashant Chaudhary, Ian A. Myles, Jordan Zeldin, Shareef Dabdoub, Varsha Deopujari, Rajiv Baveja, Robin Baker, Sarah Bengtson, Ashleigh Sutton, Shira Levy, Suchitra K. Hourigan
Journal: Allergy (2023)

While the microbiome is increasingly seen as a targetable contributor to atopic dermatitis (AD), questions remain as to whether the dysbiosis is secondary to diseased skin or if it predates symptom onset. Previous work has evaluated how the skin microbiome changes with age and established the influence of factors like delivery mode and breastfeeding on global microbiome diversity. However, these studies were unable to identify taxa which predict subsequent AD.Skin swab samples were collected from the first week of life for 72 children in the neonatal intensive care unit (NICU) at a single site hospital. Participants were followed for 3 years to determine their health status. We applied shotgun metagenomic sequencing to assess the microbiome differences between 31 children who went on to develop AD and 41 controls.We identified that subsequent development of AD was associated with differential abundance of several bacterial and fungal taxa as well as several metabolic pathways, each of which have been previously associated with active AD.Our work provides evidence of reproducibility for the previously reported dysbiotic signatures predating AD onset while also expanding prior findings through the first use of metagenomic assessment prior to AD onset. While extrapolation of our findings beyond the pre-term, NICU cohort is limited, our findings add to the evidence that the dysbiosis associated with AD pre-dates disease onset rather than reflect a secondary consequence of skin inflammation.
Nonstructural maintenance of chromatin condensin I complex subunit G promotes the progression of glioblastoma by facilitating Poly (ADP-ribose) polymerase 1-mediated E2F1 transactivation
Authors: Jianbing Hou, Pan Huang, Minghao Xu, Hao Wang, Yaqian Shao, Xuelian Weng, Yudong Liu, Hongbo Chang, Li Zhang, Hongjuan Cui
Journal: Neuro-Oncology (2023)

Abstract Background Nonstructural maintenance of chromatin condensin I complex subunit G (NCAPG), also known as non-structural maintenance of chromosomes condensin I complex subunit G, is mitosis-related protein that widely existed in eukaryotic cells. Increasing evidence has demonstrated that aberrant NCAPG expression was strongly associated with various tumors. However, little is known about the function and mechanism of NCAPG in glioblastoma (GBM). Methods The expression and prognostic value of NCAPG were detected in the clinical databases and tumor samples. The function effects of NCAPG downregulation or overexpression were evaluated in GBM cell proliferation, migration, invasion, and self-renewal in vitro and in tumor growth in vivo. The molecular mechanism of NCAPG was researched. Results We identified that NCAPG was upregulated in GBM and associated with poor prognosis. Loss of NCAPG suppressed the progression of GBM cells in vitro and prolonged survival in mouse models of GBM in vivo. Mechanistically, we revealed that NCAPG positively regulated E2F transcription factor 1 (E2F1) pathway activity. By directly interacting with Poly (ADP-ribose) polymerase 1, a co-activator of E2F1, and facilitating the PARP1-E2F1 interaction to activate E2F1 target gene expression. Intriguingly, we also discovered that NCAPG functioned as a downstream target of E2F1, which was proved by the ChIP and Dual-Luciferase results. Comprehensive data mining and immunocytochemistry analysis revealed that NCAPG expression was positively associated with the PARP1/E2F1 signaling axis. Conclusions Our findings indicate that NCAPG promotes GBM progression by facilitating PARP1-mediated E2F1 transactivation, suggesting that NCAPG is a potential target for anticancer therapy.
Chronic airflow obstruction attributable to poverty in the multinational Burden of Obstructive Lung Disease (BOLD) study
Authors: Jaymini H Patel, Andre F S Amaral, Cosetta Minelli, Fadlalla G Elfadaly, Kevin Mortimer, Asma El Sony, Karima El Rhazi, Terence A R Seemungal, Padukudru Anand Mahesh, Daniel O Obaseki, Meriam Denguezli, Rana Ahmed, Hamid Cherkaski, Parvaiz Koul, Abdul Rashid, Richard Li Cher Loh, Herve Lawin, Mohammed Al Ghobain, Asaad Ahmed Nafees, Althea Aquart-Stewart, Imed Harrabi, Sonia Buist, Peter G J Burney
Journal: Thorax (2023)

Poverty is strongly associated with all-cause and chronic obstructive pulmonary disease (COPD) mortality. Less is known about the contribution of poverty to spirometrically defined chronic airflow obstruction (CAO)—a key characteristic of COPD. Using cross-sectional data from an asset-based questionnaire to define poverty in 21 sites of the Burden of Obstructive Lung Disease study, we estimated the risk of CAO attributable to poverty. Up to 6% of the population over 40 years had CAO attributable to poverty. Understanding the relationship between poverty and CAO might suggest ways to improve lung health, especially in low-income and middle-income countries.